BACKGROUND: Increased leukocyte adhesion to brain endothelial cells forming the blood-brain barrier (BBB) precedes extravasation into the central nervous system (CNS) in neuroinflammatory diseases such as multiple sclerosis (MS). Previously, we reported that microRNA-155 (miR-155) is up-regulated in MS and by inflammatory cytokines in human brain endothelium, with consequent modulation of endothelial paracellular permeability. Here, we investigated the role of endothelial miR-155 in leukocyte adhesion to the human cerebral microvascular endothelial cell line, hCMEC/D3, under shear forces mimicking blood flow in vivo.
RESULTS: Using a gain- and loss-of-function approach, we show that miR-155 up-regulation increases leukocyte firm adhesion of both monocyte and T cells to hCMEC/D3 cells. Inhibition of endogenous endothelial miR-155 reduced monocytic and T cell firm adhesion to naïve and cytokines-induced human brain endothelium. Furthermore, this effect is partially associated with modulation of the endothelial cell adhesion molecules VCAM1 and ICAM1 by miR-155.
CONCLUSIONS: Our results suggest that endothelial miR-155 contribute to the regulation of leukocyte adhesion at the inflamed BBB. Taken together with previous observations, brain endothelial miR-155 may constitute a potential molecular target for treatment of neuroinflammation diseases.
- Blood-Brain Barrier/metabolism
- Cell Adhesion/physiology
- Cell Line
- Cerebrovascular Circulation/physiology
- Endothelial Cells/metabolism
- Enzyme-Linked Immunosorbent Assay
- Intercellular Adhesion Molecule-1/metabolism
- Jurkat Cells
- MicroRNAs/antagonists & inhibitors
- Models, Cardiovascular
- Models, Neurological
- Shear Strength/physiology
- Vascular Cell Adhesion Molecule-1/metabolism